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Biomedical subjects

E Hasegawa

Publications and source records attributed to E Hasegawa.

At least 19 recordsLinked to original sources
PubMed1995

1-Methyl-4-phenylpyridinium (MPP+) inhibits mitochondrial oxygen consumption mediated by succinate as well as malate in rat pheochromocytoma PC12 cells.

When rat pheochromocytoma PC12 cells are cultured with 1 mM 1-methyl-4-phenylpyridinium (MPP+), the number of viable cells decreases to one third in 4 days while the number increases ten-fold without MPP+. Oxygen consumption by mitochondria in the presence of malate is inhibited about 80% by the treatment of the cells with MPP+ for 4 days. Unexpectedly, succinate-dependent oxygen consumption is also inhibited to essentially the same extent as malate-dependent one. These results suggest that the impairment of the respiration mediated by succinate as well as malate is important as a mechanism of MPP(+)-induced cell death.

1-Methyl-4-phenylpyridinium↗
PubMed1993

Sulfhydryl drugs reduce neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse.

Striatal levels of dopamine and its metabolites 3-methoxy-4-hydroxy-phenylacetic acid (DOPAC) and homovanillic acid (HVA) decreased 7 days after subcutaneous injection of MPTP (20 mg/kg) to the mouse. Striatal GSH contents decreased and GSSG/GSH ratios increased one hour after subcutaneous administration of MPTP. Pretreatments of both cysteamine (200 mg/kg, s.c.) and dimercaprol (20 mg/kg, i.m.) reduced the MPTP-induced decreases in striatal dopamine, DOPAC and HVA, and also prevented the MPTP-induced decreases in GSH levels and increases in GSSG/GSH ratios. On the other hand, injection of cysteamine did not modify the MPTP-induced decreases in striatal levels of dopamine and its metabolites when it was done 2 hours after MPTP administration. Moreover, pretreatment of cysteamine did not affect striatal concentrations of MPP+ in MPTP-treated mice. These results suggest that sulfhydryl drugs such as cysteamine and dimercaprol may reduce neurotoxicity of MPTP probably via changes in redox cycle of glutathione in the brain.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

Synthesis of porphinatoirons having an alkyl amphiphilic chain and their O2 binding properties in lipid bilayers.

Synthesis and characterization of two amphiphilic tetraphenylporphinatoiron complexes having a glycerophosphocholine or an alkyl phosphoserine group are described. These porphinatoiron(II) complexes with 1-dodecyl-2-methyl-imidazole (L2MIm) were efficiently embedded in the bilayer of a phospholipid vesicle due to their high compatibility with lipids, similar to the heme substituted with four alkyl amphiphilic chains (lipid-heme). Oxygen transporting ability of the phospholipid vesicles embedded with hemes were similar to that of hemoglobin (Hb) in red blood cells.

Carbon Monoxide↗
PubMed1992

Succinate-dependent lipid peroxidation and its prevention by reduced ubiquinone in beef heart submitochondrial particles.

When succinate and ADP-Fe3+ chelate were added to beef heart submitochondrial particles pretreated with 2-thenoyltrifluoroacetone, an inhibitor of succinate dehydrogenase of the mitochondrial respiratory chain, the formation of malondialdehyde was observed. No formation was observed without the pretreatment. Oxaloacetate competitively inhibited the malondialdehyde formation with an apparent Ki of 3.4 microM. The malondialdehyde formation seemed to be initiated at the location between the p-hydroxymercuribenzoate-sensitive site and the 2-thenoyltrifluoroacetone-sensitive site of the succinate dehydrogenase because it was inhibited by the mercurial. Ubiquinone-10 was rapidly destroyed during the malondialdehyde-forming reaction when it was in the oxidized form, while the ubiquinone was not destroyed and the malondialdehyde formation was abolished when about 50% of the ubiquinone in the particles was in the reduced state. These observations suggest that the succinate-dependent peroxidation is strongly controlled by the redox state of ubiquinone.

Animals↗
PubMed1992

Oxygen-transport and solution properties of polylipid/Hb vesicles (ARC).

Polymerized phospholipid vesicle encapsulating Hb (polylipid/Hb vesicle) was prepared from a mixture of unsaturated phospholipid, cholesterol and unsaturated fatty acid and polymerization by gamma-ray irradiation. The average radius of resulting vesicles was 203 +/- 39 nm and concentrated Hb (30 wt%) was efficiently encapsulated. gamma-Ray polymerization proceeds theoretically at low temperature (4 degrees C). P50 and oxygen transporting efficiency were adjusted to 40 mmHg and 40%, respectively. Oncotic pressure and solution viscosity can be controlled to the same values as blood.

Blood Substitutes↗
PubMed1992

[Intraperitoneal chemotherapy of metastatic ovarian cancer].

Intraperitoneal chemotherapy with CDDP and other agents was instituted to treat 2 cases of metastatic ovarian cancer (developing in one case of gastric cancer and one of colon cancer). At first laparotomy, cytological examination of ascites revealed malignant cells in the 2 cases, and metastatic foci were noted in non-ovarian regions as well. Macroscopic peritoneal dissemination was apparent in the case of colon cancer. Following surgery, 5 courses of chemotherapy were given. The gastric cancer patient was treated with intraperitoneal CDDP and etoposide, while the colon cancer patient was placed on intraperitoneal CDDP therapy and continuous 5-FU iv. Clinical CR was 7 months in the former case and 10 in the latter. Although small metastatic foci were present in the posterior peritoneum in both cases at second laparotomy, distinct peritoneal dissemination had disappeared in the case of colon cancer. Cytologic examination of intraperitoneal washings proved to be negative for malignant cells in the gastric cancer case but positive in the colon cancer case. These findings indicated that although the effect was limited to clinical CR, intraperitoneal CDDP administration for metastatic ovarian cancer is effective for improving short-term prognosis.

Cisplatin↗
PubMed1991

Comparison of changes in vascular resistance between choroid and other organs following ligation of carotid artery.

The changes in the choroidal vascular resistance after carotid artery ligation were compared with those in the cerebrum and the inferior rectus muscle by evaluating the changes in the blood flow by the hydrogen clearance method. Ligation of the carotid artery produced little change in the ipsilateral cerebral blood flow, but decreased the choroidal blood flow by 16-24% and the blood flow of the inferior rectus muscle by 34-40%. Although the reduction in the arterial pressure in these organs was the same, the responses of the blood flows to the changes in the arterial pressure were different. This suggests that autoregulatory capability varies from organ to organ. It is important to study the pathogenesis of carotid artery occlusion giving special consideration to these differences among the autoregulatory capabilities of various organs.

Animals↗
PubMed1991

[Assessment of tissue platinum concentration, X-ray computed tomogram, and microangiography after CDDP intraperitoneal administration in VX2 ovarian tumor].

After intraperitoneal administration of cis-diamine-dichloroplatinum, tissue Pt concentration, dynamic CT, and microangiography were estimated in white rabbit model having been transplanted with VX2 ovarian tumor. The high Pt concentration resulting from CDDP intraperitoneal administration was recognized in kidney, liver, and VX2 ovarian tumor. CT scans demonstrated that CDDP administration inhibited the development of VX2 tumor, revealing the appearance of small areas with no enhancement corresponding to necrotic regions in the tumor external rim. A tumor time-density curve showed a significantly delayed washout of the excretory phase following CDDP administration. Regarding microangiography models, tumor vessels of less than 30 microns decreased. It was suggested that the tumor microcirculation diminished because of the increased tissue pressure concomitant with tumor necrosis.

Angiography↗
PubMed1990

Some properties of fibroblasts from a patient with debrancher deficiency.

Glycogenosis Type III is characterized by a deficiency of debranching enzyme (amylo-1,6-glucosidase, E.C. 3. 2. 1. 33) in most tissues. Low activity of liberating glucose from limited dextrin in the biopsied muscle can be demonstrated in a patient with this disease. We cultured fibroblasts from a skin biopsy from a patient with debrancher deficiency and examined the metabolism of glycogen in these cultured fibroblasts. Debrancher activity in the post-mitochondrial supernatant obtained from these fibroblasts showed a good concentration dependent manner but had approximately half of that from normal human fibroblasts (YH-1). Although the enzymatic activity of debrancher in the cultured fibroblasts from the skin was reduced essentially to the same levels as observed in muscle biopsy, little glycogen granules were accumulated in the cytoplasm of these fibroblasts as revealed by either light- or electron-microscopic observation. The fibroblasts obtained in the present study may be useful for the analysis of molecular mechanism of the debrancher deficiency disease, glycogenosis Type III.

Adolescent↗
PubMed1990

Histopathological findings in the biopsied muscle of a juvenile type III glycogenosis.

We report a case of juvenile type III glycogenosis that was confirmed by histopathological and biochemical studies. The histopathological findings consisted of vacuoles, periodic acid-Schiff positive materials, type 2B fiber deficiency, mildly positive acid phosphatase reaction and intensely positive non-specific esterase reaction. It is suggested that the enzyme reactions may be related to membrane-bound sacs containing glycogen.

Acid Phosphatase↗
PubMed1990

1-Methyl-4-phenylpyridinium (MPP+) induces NADH-dependent superoxide formation and enhances NADH-dependent lipid peroxidation in bovine heart submitochondrial particles.

We studied the effects of 1-methyl-4-phenylpyridinium (MPP+), a metabolite of a parkinsonism-inducing drug, on the superoxide formation and the lipid peroxidation in bovine heart submitochondrial particles. The NADH-supported formation of superoxide radicals was induced by MPP+ at the concentration which is considered to exist in mitochondria of dopamine neurons. The formation increased as the NADH-ubiquinone reductase activity was inhibited by MPP+. The NADH-supported lipid peroxidation by the particles in the presence of ADP-Fe3+ chelate was also enhanced by MPP+ at similar concentrations. The formation was inhibited by succinate and the reduction of endogenous ubiquinone seems to be related to the inhibition. A possibility was discussed that the formation of superoxide anions and the lipid peroxidation may contribute in the cytotoxicity of the drug.

1-Methyl-4-phenylpyridinium↗
PubMed1989

The aminoacylation of structurally variant phenylalanine tRNAs from mitochondria and various nonmitochondrial sources by bovine mitochondrial phenylalanyl-tRNA synthetase.

Bovine mitochondrial (mt) phenylalanine tRNA (tRNAPhe) was purified on a large scale using a new hybridization assay method developed by the authors. Although its melting profile suggested a loose higher order structure, presumably influenced by the apparent loss of D loop-T loop interaction necessary for forming a rigid L-shaped tertiary structure, its aminoacylation capacity catalyzed by mt phenylalanyl-tRNA synthetase (PheRS) was nearly equal to that of Escherichia coli tRNAPhe. Misaminoacylation was not observed for the mt tRNAPhe-mt PheRS system. Comparing the aminoacylation efficiencies of several combinations of tRNAPheS and PheRSs from various sources, including bovine mitochondria, bovine and yeast cytosols, E. coli, Thermus thermophilus, and Sulfolobus acidocaldarius, it was clarified that mt PheRS was able to aminoacylate all the above mentioned tRNAPhe species, albeit with varying degrees of efficiency. This broad charging spectrum suggests that mt PheRS possesses a relatively simple recognition mechanism toward its substrate, tRNAPhe.

Acylation↗
PubMed1989

[A case of multiple sclerosis with polyradiculitis and spinal subarachnoid block].

A case of 53-year-old female with multiple sclerosis was reported. In August 1987, she suffered from weakness in her legs and urinary retention. These signs had progressed with incomplete remissions and exacerbations. In March 1988, she developed sensory loss of all modalities below C2 level, spastic paralysis of upper extremities and flaccid paraplegia of lower extremities. Electromyography showed evidence of denervation in affected muscles of all extremities and paraspinal muscles. On lumber puncture, spinal fluid pressure fell to 0 mmH2O after removal of the spinal fluid of 12 ml, and the CSF protein was 740 mg/dl, indicating subarachnoid space block. The oligoclonal band was positive. MRI showed swelling in the cervical and upper thoracic cord, and multiple lesions in the periventricular white matter in the cerebrum. We diagnosed this case as multiple sclerosis in combination with acute polyradiculitis. The spinal subarachnoid block was considered to be caused by the swelling of the spinal cord.

Acute Disease↗
PubMed1988

Subunit structures of three human myeloperoxidases.

The heavy and the light subunits of human myeloperoxidase (donor: H2O2 oxidoreductase [EC 1.11.1.7]) I, II, and III were isolated from the reduced and S-carboxymethylated enzymes. These three enzymes have the same terminal amino acid sequences and similar chemical compositions in both subunits. The NH2-terminal sequences of the heavy and light subunits were determined to be Val-Asn-Cys-Glu-Thr- and Thr-Cys-Pro-Glu-Gln-, respectively; a heterogeneity was observed in the NH2-termini of the latter subunits for the three enzymes. As for COOH-termini, the sequences -(Asn, 2 Leu, Ala, Ser, Trp)-Arg-Glu-Ala and -Ala-Arg were obtained for the heavy and the light subunits, respectively. The heavy subunits contained 8-10 mol/mol of glucosamine. On the basis of these results and the amino acid sequence deduced from cDNA clones, the heavy subunits probably correspond to amino acids 279-744 and the light subunits to amino acids (164-167)-272. For the heavy subunits, Ser-745, which was predicted as the COOH-terminal amino acid from the nucleotide sequence, was removed. The light subunits were also processed at their COOH-termini by 6 residues. Four or five high mannose type carbohydrate chains were attached to the heavy subunits.

Amino Acid Sequence↗
PubMed1988

Changes in choroidal blood flow following ligation of common carotid artery.

The effects of carotid artery ligation on choroidal blood flow were studied in 30 rabbits using a hydrogen clearance method. The choroidal blood flow (ChBF) decreased significantly to about 75% for 60 minutes after the ipsilateral ligation of the common carotid artery. In 11 of the rabbits ChBF was measured both one and six weeks after ligation. ChBF recovered to 88% of the resting level one week after the ligation, and returned to the resting values six weeks after the ligation. The left carotid artery was ligated six weeks after ligation of the right carotid artery, and there was not any significant change in the ChBF of the right eye. It seemed that the recovery of the ChBF of the right eye was not through the contralateral carotid artery.

Animals↗
PubMed1987

Clearance and tissue distribution of functionalized polymeric liposomes from the blood stream of rats.

Polymeric liposomes containing a synthetic porphinato-iron-imidazole complex (hemoglobin or red blood cell model) were labeled by introducing 1,2-di[1-14C]palmitoyl-sn-glycero-3-phosphocholine into their polymerized bilayers. After intravenous injection into rats, their clearance from a blood stream was measured. The apparent half-life time (50% disappearance time) was about 14 +/- 2 h. Their tissue distribution was determined with time by whole autoradiographic measurement.

Animals↗
PubMed1987

Fibronectin's cell-adhesive domain and an amino-terminal matrix assembly domain participate in its assembly into fibroblast pericellular matrix.

Fibroblasts organize the modular cell-adhesive glycoprotein fibronectin into a highly structured pericellular matrix by poorly understood mechanisms. Previous studies implicated an amino-terminal domain in matrix assembly and suggested that fibronectin's cell-adhesive domain and the corresponding fibroblast receptor were not involved in this process. To further elucidate the fibronectin region(s) involved in matrix assembly, we mapped a library of proteolytic fragments and antibodies to various fibronectin domains. The fragments and antibodies were used to probe the role of fibronectin's amino-terminal and cell-adhesive domains in a fibroblast matrix assembly assay. We found that fibronectin fragments including the first 25-kDa sequence of fibronectin and antibodies to amino-terminal domains inhibited pericellular matrix assembly. Polyclonal antibodies to the 40-kDa collagen binding domain following the 25-kDa amino-terminal domain also inhibited matrix assembly. However, collagen binding is not required for matrix assembly as neither monoclonals blocking collagen binding nor purified collagen binding domains themselves inhibited matrix assembly. Therefore, the amino-terminal region of fibronectin contains a site important in matrix assembly, and most activity is present in the first 25-kDa of fibronectin. Fibronectin's cell-adhesive domain and the fibroblast receptor binding to this domain also play an important role in fibronectin matrix assembly. Apart from a monoclonal antibody to the amino-terminal domain, only monoclonal antibodies binding to fibronectin's cell-adhesive domain and inhibiting cell adhesion also inhibited matrix assembly. In addition a 105-kDa fragment containing the cell-adhesive domain inhibited matrix assembly. We conclude that at least two discrete and widely separated sites in fibronectin with different binding properties--the carboxyl-terminal fibroblast cell-adhesive domain and an amino-terminal matrix assembly domain localized primarily within the first 25 kDa--are required for fibronectin pericellular matrix assembly by fibroblasts. Fibronectin's cell-adhesive domain and its cell surface-receptor complex appear to be involved in the matrix assembly process prior to a step involving the amino-terminal domain. We believe that this step is likely to be the initiation of cell-associated fibronectin fibril formation by the fibronectin-adhesive-receptor complex.

Amino Acid Sequence↗